Abstract This application is being submitted in response to NOT-AI-18-055. As the opioid crisis grows, novel treatments for opioid use disorder are desperately needed. Opioid vaccines that elicit high titer, long-lasting antibodies that block opioid drug activity are a promising treatment approach. However, eliciting high titer antibodies to a small molecule is challenging. In this proposal, we will use a highly immunogenic, multivalent virus-like particle (VLP) platform to develop vaccines targeting opioid drugs. First, we will make derivatives of opioid drugs such that they can be chemically conjugated at high density on VLPs derived from Qbeta bacteriophage. The immunogenicity of these vaccines will then be assessed in mice. In this one-year period covered by this supplement application, we will measure the titers of antibodies elicited by our vaccines, assess the longevity of the antibody response, and determine the optimal dosing and immunization schedule. Our goal is to achieve long-lasting and high titer antibodies to opioid drugs of abuse.